Drug trial of drug that reduced Lp(a) fails

(Bob M) #1

Lp(a) is the latest in a series of “bad” “cholesterol” that is believed to cause heart disease. They tested a drug that lowered Lp(a), but had little effect on heart disease:

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It’s the problem that occurs with LDL (another “bad” “cholesterol”) and ApoB (yet another bad cholesterol), where many people with high versions of these do not have heart disease. There are drugs (like statins) that lower LDL, but some believe statins work not by lowering LDL but through other mechanisms (such as increasing nitric oxide and/or improving endothelial health).

There are other Lp(a) drugs in the pipeline, but if there is a drug that reduces Lp(a) by 80% yet doesn’t help with heart disease, if those other drugs work, that means to me that they don’t work by lowering Lp(a).

(Joey) #2

Perhaps the simplest explanation as to why lowering Lp(a) has not produced lower incidences of adverse CV events is because Lp(a) is a symptom of heart disease … not a cause.

It’s the old “firetrucks arriving at a fire” analogy all over again. Limiting firetruck response is not a great strategy to reduce damage.

If cholesterol, in its various forms, is a reflection of inflammation, not its cause, then lowering its presence is like trying to fight a fire with air conditioners… to reduce the observable heat.

(Bob M) #3

In this case, Lp(a) is primarily genetic. For instance, the “good” is 75 nmol/l, and mine has often been over 300. 4 times as much.

My personal opinion is that none of Lp(a), LDL, ApoB is causal. I think something causes an injury to the endothelium/glycocalyx where injury > repair. Lp(a) MIGHT be more problematic once there is an injury, as it does appear to be “stickier”.

But I think you’re correct in that things like inflammation, which is primarily caused by poor metabolic health, is a problem.

But I had a CAC score of zero 6 or so years ago, and now I have a score of 30 while being keto and maintaining the best diet/exercise I can do. Personally, I think this is due to covid (or possibly the flu or both), because I get a lung scan done (saw a spot when I got my CAC scan), and there was damage there my doc said was probably related to a virus. That damage was also new. Age doesn’t help, either. :wink: